Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10−10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10−8 ). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10−11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure

Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10−10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10−8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10−11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure

Genomic Insights into the Formation of Human Populations in East Asia

厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室王传超教授课题组与哈佛医学院David Reich教授团队合作，联合全球43个单位的85位共同作者组成的国际合作团队通过古DNA精细解析东亚人群形成历史。研究人员利用古DNA数据检验了东亚地区农业和语言共扩散理论，综合考古学、语言学等证据，该研究系统性地重构了东亚人群的形成、迁徙和混合历史。这是目前国内开展的东亚地区最大规模的考古基因组学研究，此次所报道的东亚地区古人基因组样本量是以往国内研究机构所发表的样本量总和的两倍，改变了东亚地区尤其是中国境内考古基因组学研究长期滞后的局面。 该研究是由王传超教授团队与哈佛医学院（David Reich教授）、德国马普人类历史科学研究所（Johannes Krause教授）、复旦大学现代人类学教育部重点实验室（李辉教授和金力院士）、维也纳大学进化人类学系（Ron Pinhasi副教授）、南洋理工大学人文学院（Hui-Yuan Yeh助理教授）、俄罗斯远东联邦大学科学博物馆（Alexander N Popov研究员）、西安交通大学（张虎勤教授）、蒙古国国家博物馆研究中心、乌兰巴托国立大学考古系、华盛顿大学人类学系、台湾成功大学考古所、加州大学人类学系等全球43个单位的85位共同作者组成的国际合作团队联合完成的。厦门大学人类学研究所、厦门大学生命科学学院细胞应激生物学国家重点实验室为论文第一完成单位。厦门大学人类学研究所韦兰海副教授、胡荣助理教授、郭健新博士后、何光林博士后和杨晓敏硕士参与了研究工作。The deep population history of East Asia remains poorly understood due to a lack of ancient DNA data and sparse sampling of present-day people1,2. We report genome-wide data from 166 East Asians dating to 6000 BCE-1000 CE and 46 present-day groups. Hunter-gatherers from Japan, the Amur River Basin, and people of Neolithic and Iron Age Taiwan and the Tibetan plateau are linked by a deeply-splitting lineage likely reflecting a Late Pleistocene coastal migration. We follow Holocene expansions from four regions. First, hunter-gatherers of Mongolia and the Amur River Basin have ancestry shared by Mongolic and Tungusic language speakers but do not carry West Liao River farmer ancestry contradicting theories that their expansion spread these proto-languages. Second, Yellow River Basin farmers at ～3000 BCE likely spread Sino-Tibetan languages as their ancestry dispersed both to Tibet where it forms up ～84% to some groups and to the Central Plain where it contributed ～59-84% to Han Chinese. Third, people from Taiwan ～1300 BCE to 800 CE derived ～75% ancestry from a lineage also common in modern Austronesian, Tai-Kadai and Austroasiatic speakers likely deriving from Yangtze River Valley farmers; ancient Taiwan people also derived ～25% ancestry from a northern lineage related to but different from Yellow River farmers implying an additional north-to-south expansion. Fourth, Yamnaya Steppe pastoralist ancestry arrived in western Mongolia after ～3000 BCE but was displaced by previously established lineages even while it persisted in western China as expected if it spread the ancestor of Tocharian Indo-European languages. Two later gene flows affected western Mongolia: after ～2000 BCE migrants with Yamnaya and European farmer ancestry, and episodic impacts of later groups with ancestry from Turan.We thank David Anthony, Ofer Bar-Yosef, Katherine Brunson, Rowan Flad, Pavel Flegontov,Qiaomei Fu, Wolfgang Haak, Iosif Lazaridis, Mark Lipson, Iain Mathieson, Richard Meadow,Inigo Olalde, Nick Patterson, Pontus Skoglund, Dan Xu, and the four reviewers for valuable comments. We thank Naruya Saitou and the Asian DNA Repository Consortium for sharing genotype data from present-day Japanese groups. We thank Toyohiro Nishimoto and Takashi Fujisawa from the Rebun Town Board of Education for sharing the Funadomari Jomon samples, and Hideyo Tanaka and Watru Nagahara from the Archeological Center of Chiba City who are excavators of the Rokutsu Jomon site. The excavations at Boisman-2 site (Boisman culture), the Pospelovo-1 site (Yankovsky culture), and the Roshino-4 site (Heishui Mohe culture) were funded by the Far Eastern Federal University and the Institute of History,Archaeology and Ethnology Far Eastern Branch of the Russian Academy of Sciences; research on Pospelovo-1 is funded by RFBR project number 18-09-40101. C.C.W was funded by the Max Planck Society, the National Natural Science Foundation of China (NSFC 31801040), the Nanqiang Outstanding Young Talents Program of Xiamen University (X2123302), the Major project of National Social Science Foundation of China (20&ZD248), a European Research Council (ERC) grant to Dan Xu (ERC-2019-ADG-883700-TRAM) and Fundamental Research Funds for the Central Universities (ZK1144). O.B. and Y.B. were funded by Russian Scientific Foundation grant 17-14-01345. H.M. was supported by the grant JSPS 16H02527. M.R. and C.C.W received funding from the ERC under the European Union’s Horizon 2020 research and innovation program (grant No 646612) to M.R. The research of C.S. is supported 30 by the Calleva Foundation and the Human Origins Research Fund. H.L was funded NSFC (91731303, 31671297), B&R International Joint Laboratory of Eurasian Anthropology (18490750300). J.K. was funded by DFG grant KR 4015/1-1, the Baden Württemberg Foundation, and the Max Planck Institute. Accelerator Mass Spectrometry radiocarbon dating work was supported by the National Science Foundation (NSF) (BCS-1460369) to D.J.K. and B.J.C. D.R. was funded by NSF grant BCS-1032255, NIH (NIGMS) grant GM100233, the Paul M. Allen Frontiers Group, John Templeton Foundation grant 61220, a gift from Jean-Francois Clin, and the Howard Hughes Medical Institute. 该研究得到了国家自然科学基金“中国东南各族群的遗传混合”、国家社科基金重大项目“多学科视角下的南岛语族的起源和形成研究”、厦门大学南强青年拔尖人才支持计划A类、中央高校基本科研业务费等资助

Effects of Water-Saving Irrigation on Hydrological Cycle in an Irrigation District of Northern China

In an arid and semi-arid irrigation district, water-saving practices are essential for the sustainable use of water resources. The Soil and Water Assessment Tool (SWAT) was used to simulate hydrological processes under three water-saving scenarios for the Jinghui Canal irrigation district (JCID) in Northwest China. Due to the lack of available hydrometric stations in the study area, the model was calibrated by Moderate Resolution Imaging Spectroradiometer Global Evaporation (MOD16) from 2001 to 2010 on monthly scale. The simulation results showed that using MOD16 to calibrate the SWAT model was an alternative approach when hydro-meteorological data were lacking. It also revealed that the annual average surface runoff (SURQ) decreased by 4.13%, 8.37% and 12.08% and the percolation (PERC) increased by 3.67%, 7.59% and 11.19%, with the improvement of the water-saving degree (the effective utilization coefficient of irrigation water (EUCIW) increased by 0.1, 0.2 and 0.3). Compared with the above two components, the change in actual evapotranspiration (ET) was not obvious. From the perspective of the spatial scale, the changes in every component in the east regions were generally greater than those in the west regions. On a monthly scale, the change in every component was mainly during these two periods. The analysis results of water balance in the study area showed that the proportion of SURQ in water balance decreased (from 14.02% to 12.33%), while that of PERC increased (from 10.99% to 12.22%) after the application of the water-saving irrigation. The decrease in the variation in soil water content indicates that the improvement of the water-saving degree plays a positive role in maintaining the sustainable development of water resources in irrigated areas. This study demonstrates the potential to use remotely sensed evapotranspiration data for hydrological model calibration and validation in a sparsely gauged region with reasonable accuracy. The results of this study also provide a reference for the effect of water-saving irrigation in the irrigated area

Groundwater Depth Forecasting Using a Coupled Model

Accurate and reliable prediction of groundwater depth is a critical component in water resources management. In this paper, a new method based on coupling wavelet decomposition method (WA), autoregressive moving average (ARMA) model, and BP neural network (BP) model for groundwater depth forecasting applications was proposed. The relative performance of the proposed coupled model (WA-ARMA-BP) was compared to the regular autoregressive integrated moving average (ARIMA) and BP models for annual average groundwater depth forecasting using leave-one-out cross-validation (LOO-CV). The variables used to develop and validate the models were average groundwater depth data recorded from 1981 to 2010 in Jinghui Canal Irrigation District in the northwest of China. It was found that the WA-ARMA-BP model provided more accurate annual average groundwater depth forecasts compared to the ARIMA and BP models. The results of the study indicate the potential of the WA-ARMA-BP model in forecasting nonstationary time series such as groundwater depth

Changes in Different Classes of Precipitation and the Impacts on Sediment Yield in the Hekouzhen-Longmen Region of the Yellow River Basin, China

The sediment yield of the Yellow River Basin has obviously decreased since the 1980s, and the impacts of precipitation on sediment yield changes have become increasingly important with the global climate change. The spatial and temporal variations in annual precipitation and different classes of precipitation in the Hekouzhen-Longmen region (HLR) in the middle reaches of the Yellow River Basin were investigated using data collected from 301 rainfall stations from 1966 to 2016. The impacts of precipitation variation on sediment yield were evaluated, and the hydrological modeling method was used to quantitatively assess the attribution of precipitation and other factors to sediment yield changes in the HLR. The results show that the annual precipitation and P10 increased from the northwest to the southeast of the HLR, suggesting it was drier in the northwest region of the HLR. P25 and P50 were mainly concentrated in the northwestern and southwestern parts of the HLR, reflecting that heavy rain was more likely to occur in these regions of the HLR. All of the annual precipitation and different classes of precipitation had no significant changing trends from 1966 to 2016, and the relationship between rainfall and sediment yield obviously changed in 2006. Compared with the average annual mean values from 1966 to 2016, both the annual precipitation and the different classes of precipitation were higher in the HLR during 2007–2016. The sediment yield decrease during 1990–1999 was mainly influenced by precipitation, while other factors were the main driving factor for the sediment yield decrease in the periods of 1980–1989, 2000–2009, and 2010–2016, and other factors have become the dominant driving factors of the sediment yield change in the HLR since 2000

Electron Beam Welding and Post Heat Treatment of a New Near-Beta High-Strength Ti-4Al-5Mo-5V-5Cr-1Nb Alloy

Ti-4Al-5Mo-5V-5Cr-1Nb (wt.%) is a new type of high-strength (~1300 MPa) titanium (Ti) alloy developed for aerospace applications. Until now, the research on its welding and subsequent heat treatment is barren. Herein, we employed electron beam welding (EBW) to a solutionized Ti-4Al-5Mo-5V-5Cr-1Nb with a phase constituent of α + β and investigated its microstructure and mechanical properties in both as-welded (AW) and post-weld aging treated (PWAT) conditions. Results showed that due to the thermal input of the welding process, the α phase in the original microstructure of base material (BM) transformed into the β phase in the fusion zone (FZ). Similar microstructural evolution was observed for the heat-affected zone (HAZ) near the FZ (Near-HAZ), whereas the HAZ far away from FZ (Far-HAZ) contained a small amount of round α phase (ghost α) due to its slower cooling rate. Such a microstructural change resulted in poor tensile strength (~780 Mpa) for the as-welded joint. After PWAT, a large number of acicular α precipitated in the FZ and HAZ and its size (S) in different zones followed the order of SFar-HAZ FZ ≈ SNear-HAZ BM. The presence of αs precipitates remedied the tensile strength of the weld joint almost to the same as that of the BM. The present findings established the foundation of the application of this high-strength Ti alloy